Abstract

ADIPONECTIN GENE POLYMORPHISMS AND CARDIOVASCULAR DISEASE

Nitin Tyagi*, Parmila Dudi, Anu R.I., Subhra Sucharita Sahoo, Alka Ramteke and Charanjeet Kaur

ABSTRACT

Cardiovascular diseases (CVD) have been leading cause of morbidity and mortality in India. CVDs account for around half of the death resulting from non-communicable diseases (NCDs). Recent trends indicate that the disease has escalated to younger age groups also. The present evidence suggests an average mortality of 4% in the age group of 20-49 years and 6% in those above 50 years due to CVD. According to a WHO report, the current age standardized CVD mortality rates among males and females in India (per 100,000) are 363-443 and 181- 281 respectively. Cardiovascular disease mediated by atherosclerosis is initiated very early in human life and manifests itself clinically after a long latent phase of integrative and cumulative insults to the vessel wall by genetic, environmental, behavioral, and dietary risk factors. Despite the proven existence and influence of traditional risk factors, there are a number of other risk factors that play a significant role in development in Atherosclerotic Cardiovascular Diseases. Adiponectin is one among them. Adiponectin (Ad), a 30-kDa peptide hormone, is almost exclusively secreted by adipose tissue. It plays an important role in the regulation of lipid metabolism and glucose metabolism. Adiponectin is an adipocyte derived peptide which isalso known as GBP 28, Acrp30, AdipoQ and apM1.Ithas been proven to have a role in prevention of development of atherosclerosis by inhibiting vascular adhesion factors in endothelial cells inhibiting foam cell formation, suppressing growth and function of macrophages. In numerous trials, patients with serum Adiponectin levels below 4μg/ml has been shown to have association with obesity linked metabolic and cardiovascular disorders including Coronary artery Disease, Insulin resistance, Type 2 diabetes, lipodystrophy, Non Alcoholic Hepatic Steatosis & Hypertension. Adiponectin also influences IL-10 levels which is an anti-inflammatory cytokine. IL-10 protects against atherosclerosis by exerting an anti- apoptotic and anti-inflammatory action causing down regulation of Th1 response, inhibiting matrix degrading Matrix Metalloproteins (MMPs) and tissue factor(TF) thereby preventing plaque instability. Adiponectin induces expression of IL-10 in human macrophages which then mediates its anti-atherogenic properties. Adiponectin also increases expression of TIMP(tissue inhibitor of metalloproteinases) by upregulating IL-10 synthesis thereby providing an anti-atherogenic local environment. Adiponectin is synthesized by Adiponectin gene located on chromosome 3q27. Recently, several single-nucleotide polymorphisms of the Ad gene, such as rs266729 (C > G) and rs2241766 (T > G), were shown to be significantly associated with CAD. Few single nucleotide polymorphisms (SNPs) in the Adiponectin gene have been studied worldwide and shown to be associated with low Adiponectin levels and thereby contribute to increased risk of development of coronary artery disease.

Keywords: Cardiovascular diseases Adiponectin coronary artery disease.